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      Treatment of laryngopharyngeal reflux disease: A systematic review

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          Abstract

          BACKGROUNG

          For a long time, laryngopharyngeal reflux disease (LPRD) has been treated by proton pump inhibitors (PPIs) with an uncertain success rate.

          AIM

          To shed light the current therapeutic strategies used for LPRD in order to analysis the rationale in the LPRD treatment.

          METHODS

          Three authors conducted a PubMed search to identify papers published between January 1990 and February 2019 about the treatment of LPRD. Clinical prospective or retrospective studies had to explore the impact of medical treatment(s) on the clinical presentation of suspected or confirmed LPRD. The criteria for considering studies for the review were based on the population, intervention, comparison, and outcome framework.

          RESULTS

          The search identified 1355 relevant papers, of which 76 studies met the inclusion criteria, accounting for 6457 patients. A total of 64 studies consisted of empirical therapeutic trials and 12 were studies where authors formally identified LPRD with pH-monitoring or multichannel intraluminal impedance-pH monitoring (MII-pH). The main therapeutic scheme consisted of once or twice daily PPIs for a duration ranged from 4 to 24 wk. The most used PPIs were omeprazole, esomeprazole, rabeprazole, lansoprazole and pantoprazole with a success rate ranging from 18% to 87%. Other composite treatments have been prescribed including PPIs, alginate, prokinetics, and H 2 Receptor antagonists.

          CONCLUSION

          Regarding the development of MII-pH and the identification of LPRD subtypes (acid, nonacid, mixed), future studies are needed to improve the LPRD treatment considering all subtypes of reflux.

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          Most cited references102

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          The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury.

          J Koufman (1991)
          Occult (silent) gastroesophageal reflux disease (GER, GERD) is believed to be an important etiologic factor in the development of many inflammatory and neoplastic disorders of the upper aerodigestive tract. In order ot test this hypothesis, a human study and an animal study were performed. The human study consisted primarily of applying a new diagnostic technique (double-probe pH monitoring) to a population of otolaryngology patients with GERD to determine the incidence of overt and occult GERD. The animal study consisted of experiments to evaluate the potential damaging effects of intermittent GER on the larynx. Two hundred twenty-five consecutive patients with otolaryngologic disorders having suspected GERD evaluated from 1985 through 1988 are reported. Ambulatory 24-hour intraesophageal pH monitoring was performed in 197; of those, 81% underwent double-probe pH monitoring, with the second pH probe being placed in the hypopharynx at the laryngeal inlet. Seventy percent of the patients also underwent barium esophagography with videofluoroscopy. The patient population was divided into seven diagnostic subgroups: carcinoma of the larynx (n = 31), laryngeal and tracheal stenosis (n = 33), reflux laryngitis (n = 61), globus pharyngeus (n = 27), dysphagia (n = 25), chronic cough (n = 30), and a group with miscellaneous disorders (n = 18). The most common symptoms were hoarseness (71%), cough (51%), globus (47%), and throat clearing (42%). Only 43% of the patients had gastrointestinal symptoms (heartburn or acid regurgitation). Thus, by traditional symptomatology, GER was occult or silent in the majority of the study population. Twenty-eight patients (12%) refused or could not tolerate pH monitoring. Of the patients undergoing diagnostic pH monitoring, 62% had abnormal esophageal pH studies, and 30% demonstrated reflux into the pharynx. The results of diagnostic pH monitoring for each of the subgroups were as follows (percentage with abnormal studies): carcinoma (71%), stenosis (78%), reflux laryngitis (60%), globus (58%), dysphagia (45%), chronic cough (52%), and miscellaneous (13%). The highest yield of abnormal pharyngeal reflux was in the carcinoma group and the stenosis group (58% and 56%, respectively). By comparison, the diagnostic barium esophagogram with videofluoroscopy was frequently negative. The results were as follows: esophagitis (18%), reflux (9%), esophageal dysmotility (12%), and stricture (3%). All of the study patients were treated with antireflux therapy. Follow-up was available on 68% of the patients and the mean follow-up period was 11.6 +/- 12.7 months.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole.

            Nonacid reflux may explain symptoms in acid-suppressed patients. Simultaneous intraesophageal impedance and pH measurement was used to evaluate the frequencies of postprandial acid and nonacid reflux before and after omeprazole administration. Twelve heartburn patients underwent two 2-hour studies of intraesophageal impedance and pH in the right lateral decubitus position after a refluxogenic meal; session 1 without medication, session 2 after 7 days of omeprazole twice daily. Acid and nonacid reflux were quantified. Two hundred seventeen reflux episodes were detected before and 261 after omeprazole treatment (P > 0.05). Percentage of acid reflux decreased (from 45% to 3%, P = 0.02) and nonacid reflux increased (from 55% to 97%, P = 0.03) after omeprazole. Heartburn and acid taste were more commonly linked to acid reflux but were also produced by nonacid reflux. Regurgitation was reported equally in acid and nonacid reflux. Delta(pH) > 1 did not help predict the presence of symptoms during nonacid reflux. During treatment with omeprazole, postprandial reflux becomes predominantly nonacid. Symptoms are more common with acid reflux but are also produced by nonacid reflux. Simultaneous intraesophageal impedance and pH may be useful in evaluating the role of nonacid reflux in symptoms that persist despite adequate acid suppression.
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              Evaluation and management of laryngopharyngeal reflux.

              Laryngopharyngeal reflux (LPR) is a major cause of laryngeal inflammation and presents with a constellation of symptoms different from classic gastroesophageal reflux disease. To provide a practical approach to evaluating and managing cases of LPR. The PubMed database and the Ovid Database of Systematic Reviews were systematically searched for laryngopharyngeal reflux, laryngopharyngeal reflux fundoplication, laryngopharyngeal reflux PPI treatment, and gastroesophageal reflux AND laryngitis. Pertinent subject matter journals and reference lists of key research articles were also hand-searched for articles relevant to the analysis. Reflux of gastric contents is a major cause of laryngeal pathology. The pathophysiology and symptom complex of LPR differs from gastroesophageal reflux disease. Laryngeal pathology results from small amounts of refluxate--typically occurring while upright during the daytime--causing damage to laryngeal tissues and producing localized symptoms. Unlike classic gastroesophageal reflux, LPR is not usually associated with esophagitis, heartburn, or complaints of regurgitation. There is no pathognomonic symptom or finding, but characteristic symptoms and laryngoscopic findings provide the basis for validated assessment instruments (the Reflux Symptom Index and Reflux Finding Score) useful in initial diagnosis. There are 3 approaches to confirming the diagnosis of LPR: (1) response of symptoms to behavioral and empirical medical treatment, (2) endoscopic observation of mucosal injury, and (3) demonstration of reflux events by impedance and pH-monitoring studies and barium swallow esophagram. While pH monitoring remains the standard for confirming the diagnosis of gastroesophageal reflux, the addition of multichannel intraluminal impedance technology improves diagnostic accuracy for describing LPR events. Ambulatory multichannel intraluminal impedance assessment allows for identification of gaseous as well as liquid refluxate and detection of nonacid reflux events that are likely significant in confirming LPR. Although some patients respond to conservative behavioral and medical management, as is the case with gastroesophageal reflux, most require more aggressive and prolonged treatment to achieve regression of symptoms and laryngeal tissue changes. Surgical intervention such as laparoscopic fundoplication is useful in selected recalcitrant cases with laxity of the gastroesophageal sphincter. Laryngopharyngeal reflux should be suspected when the history and laryngoscopy findings are suggestive of the diagnosis. Failure to respond to a 3-month trial of behavioral change and gastric acid suppression by adequate doses of proton pump inhibitor medication dictates need for confirmatory studies. Multichannel intraluminal impedance and pH-monitoring studies are most useful in confirming LPR and assessing the magnitude of the problem.
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                6 October 2019
                6 October 2019
                : 7
                : 19
                : 2995-3011
                Affiliations
                Laboratory of Anatomy and Cell Biology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons 7000, Belgium
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France. jerome.lechien@ 123456umons.ac.be
                Department of Otolaryngology-Head and Neck Surgery, CHU de Lille, Lille 59000, France
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Division of Phoniatrics and Audiology, Department of Mental and Physical Health and Preventive Medicine, University of L. Vanvitelli, Naples 80100, Italy
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                ENT Audiology and Phoniatric Unit, University of Pisa, Pisa 56100, Italy
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Larynx Function and Acoustic Voice Laboratory, Department of Speech Therapy, School of Rehabilitation, Tehran 11369, Iran
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Department of Otolaryngology, Marmara University Pendik Training and Research Hospital, Istanbul 34722, Turkey
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Department of Otology, Neurotology and Skullbase Surgery, Madras ENT Research Foundation, Tamil Nadu 60028, India
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Department of Otorhinolaryngology and Head and Neck Surgery, Hospital Complex of Santiago de Compostela, Santiago de Compostela 15700, Spain
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Department of Otorhinolaryngology and Head and Neck Surgery, Kyung Hee University Medical Center, Seoul 130702, Korea
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Laboratory of Anatomy and Cell Biology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons 7000, Belgium
                Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies, Paris 75000, France
                Author notes

                Author contributions: Lechien JR, Mouawad F, Saussez S, Eun Y substantial contributed to the conception or design of the work; made the acquisition, analysis, or interpretation of data for the work; drafted the work; made final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Barillari M and Calvo-Henriquez C substantial contributed to the conception or design of the work; made the acquisition (systematic review performing); made the interpretation of data; agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Khoddami SM, Raghunandhan SK, Enver N, Nacci A made the interpretation of data, discussion improvement, agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

                Corresponding author: Jerome R Lechien, MD, MSc, PhD, Associate Professor, Laboratory of Anatomy and Cell Biology, Faculty of Medicine, University of Mons (UMONS), Avenue du Champ de mars, 6, Mons B7000, Belgium. jerome.lechien@ 123456umons.ac.be

                Telephone: +32-65-373584

                Article
                jWJCC.v7.i19.pg2995
                10.12998/wjcc.v7.i19.2995
                6795731
                31624747
                85bd5677-f192-440e-84f3-c00948ef9355
                ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 28 March 2019
                : 5 September 2019
                : 11 September 2019
                Categories
                Systematic Review

                laryngopharyngeal,reflux,laryngitis,treatment,proton pump inhibitors

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